Lipooligosaccharide (LOS) is one of the major surface antigens of Neisseria meningitidis and can be divided into 12 immunotypes. We have been investigating the potential use of detoxified LOS as a vaccine against group B meningococcal infections. The LOS was isolated from N. meningitidis strain 7880 (L10) and detoxified with hydrazine to reduce its toxicity to clinically acceptable levels. The detoxified LOS (dLOS) was coupled to tetanus toxoid (TT) through a linker of adipic acid dihydrazide to form a dLOS-TT conjugate. The conjugate was immunogenic in mice and rabbits and induced high levels of IgG antibody to the LOS. Immunogenicity of the conjugate in both animals was enhanced by monophosphoryl lipid A plus trehalose dimycolate as an adjuvant. The resulting rabbit antisera also showed complement-mediated bactericidal activities against the homologous L10 strain and heterologous L5, L7, and L8 strains. The same approach was also used to prepare the dLOS-protein conjugates from a strain of nontypable Haemophilus influenzae which causes otitis media in infants and children with similar results. These results indicate that the detoxified LOS-protein conjugates are possible vaccine candidates.